Retinal ganglion cell repopulation for vision restoration in optic neuropathy: a roadmap from the RReSTORe Consortium
Authors: Jonathan R. Soucy, Erika A. Aguzzi, Julie Cho, Michael James Gilhooley, Casey Keuthan, Ziming Luo, Aboozar Monavarfeshani, Meher A. Saleem, Xue-Wei Wang, Juilette Wohlschlegel, Abdelrahman Y. Fouda, Ajay Ashok, Ala Moshiri, Alain Chedotal, Amberlynn A. Reed, Amjad Askary, An-Jey A. Su, Anna La Torre, Archana Jalligampala, Ariadna Silva-Lepe, Arupratan Das, Barbara Wirostko, Benjamin J. Frankfort, Benjamin Sivyer, Bhagwat Alapure, Brent Young, Brian Clark, Bryan William Jones, Chase Hellmer, Claire Mitchell, Claire Ufongene, Dan Goldman, David Feldheim, David H. Gutmann, David J. Calkins, David Krizaj, David M. Gamm, Diana C. Lozano, Diane E. Bovenkamp, Dong Feng Chen, Elena Vecino Cordero, Ephraim F. Trakhtenberg, Feng Tian, Fengquan Zhou, Gillian J. McLellan, Harry A. Quigley, Hashem Abu Serhan, James R. Tribble, Jason Meyer, Jeff Gross, Jeff S. Mumm, Jeremy M. Sivak, Jingliang Simon Zhang, Jiun L. Do, Jonathan Crowston, Julie Chen, Juliette McGregor, Kalyan C. Vinnakota, Kang-Chieh Huang, Karen Peynshaert, Katherine E. Uyhazi, Keith Martin, Ken Muller, Kevin K. Park, Kin-Sang Cho, Kun-Che Chang, Larry Benowitz, Leonard A. Levin, Levi Todd, Lies De Groef, Lieve Moons, Luis Alarcon-Martinez, Mandeep S. Singh, Manuel Vidal-Sanz, Mariana S. Silveira, Marina Pavlou, Matthew B. Veldman, Matthew Van Hook, Melanie Samuel, Mengming Hu, Micalla Peng, Michael Young, Michel Cayouette, Mohammad H. Geranmayeh, Mollie Woodworth, Monica Vetter, Nicholas R. Marsh-Armstrong, Pete A. Williams, Pratheepa Kumari Rasiah, Preeti Subramanian, Qi N. Cui, Rebecca M. Sappington, Reem Amine, Richard Eva, Robert J. Johnston, Roman J. Giger, Ross Ethier, Sadaf Abed, Sehrish Nizar Ali Momin, Seth Blackshaw, Shane A. Liddelow, Stella Mary, Stephen Atolagbe, Supraja Varadarajan, Tareq I. Nabhan, Tasneem Khatib, Tasneem Putliwala Sharma, Thomas Brunner, Tom Greenwell, Tonia S. Rex, Trent Watkins, Tudor C. Badea, V. Vrathasha, Venkata Ramana Murthy Chavali, Viviane M. Oliveira-Valença, Wai Lydia Tai, Wyndham M. Batchelor, Xian-Jie Yang, Yong Park, Yuan Pan, Petr Baranov, Adriana Di Polo, Brad Fortune, Kimberly K. Gokoffski, Jeffrey L. Goldberg, William Guido, Alex L. Kolodkin, Carol A. Mason, Yvonne Ou, Thomas A. Reh, Ahmara G. Ross, Brian C. Samuels, Derek Welsbie, Donald J. Zack, Thomas V. Johnson
Journal: Molecular Neurodegeneration (2023)

Retinal ganglion cell (RGC) death in glaucoma and other optic neuropathies results in irreversible vision loss due to the mammalian central nervous system's limited regenerative capacity. RGC repopulation is a promising therapeutic approach to reverse vision loss from optic neuropathies if the newly introduced neurons can reestablish functional retinal and thalamic circuits. In theory, RGCs might be repopulated through the transplantation of stem cell-derived neurons or via the induction of endogenous transdifferentiation. The RGC Repopulation, Stem Cell Transplantation, and Optic Nerve Regeneration (RReSTORe) Consortium was established to address the challenges associated with the therapeutic repair of the visual pathway in optic neuropathy. In 2022, the RReSTORe Consortium initiated ongoing international collaborative discussions to advance the RGC repopulation field and has identified five critical areas of focus: (1) RGC development and differentiation, (2) Transplantation methods and models, (3) RGC survival, maturation, and host interactions, (4) Inner retinal wiring, and (5) Eye-to-brain connectivity. Here, we discuss the most pertinent questions and challenges that exist on the path to clinical translation and suggest experimental directions to propel this work going forward. Using these five subtopic discussion groups (SDGs) as a framework, we suggest multidisciplinary approaches to restore the diseased visual pathway by leveraging groundbreaking insights from developmental neuroscience, stem cell biology, molecular biology, optical imaging, animal models of optic neuropathy, immunology & immunotolerance, neuropathology & neuroprotection, materials science & biomedical engineering, and regenerative neuroscience. While significant hurdles remain, the RReSTORe Consortium's efforts provide a comprehensive roadmap for advancing the RGC repopulation field and hold potential for transformative progress in restoring vision in patients suffering from optic neuropathies.